Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status (DICER) in COVID-19 (DICER)

The most severe manifestations of COVID-19 include respiratory failure, coagulation problems, and death. Inflammation and blood clotting are believed to play an important role in these manifestations. Research in humans has shown that dipyridamole can reduce blood clotting. This research study is being conducted to learn whether 14 days of treatment with dipyridamole will reduce excessive blood clotting in COVID-19.

This study will enroll participants with confirmed coronavirus (SARS-CoV)-2 infection that are admitted. Eligible participants will be randomized to receive dipyridamole or placebo for 14 days in the hospital. In addition, data will be collected from the medical record, and there will also be blood draws during the hospitalization.

Study Overview

• Status: Completed
• Conditions: Covid-19; COVID; Corona Virus Infection; SARS-CoV-2 Infection
• Intervention / Treatment: Drug: Dipyridamole 100 Milligram(mg); Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide informed consent prior to performing study procedures unless they have a legally authorized representative (LAR)
• Confirmed coronavirus (SARS-CoV-2) infection
• Currently hospitalized or anticipated hospitalization requiring supplemental oxygen

Exclusion Criteria:

• In the opinion of at least two investigators, unlikely to survive for >48 hours from screening
• Concurrent enrollment in a clinical trial with a cytokine inhibitor (targeting interleukin-6 (IL-6), Interleukin-6 Receptor (IL-6R), IL-1, or Janus kinase). Use of remdesivir is permitted.
• Currently on invasive mechanical ventilation.
• Hypotension defined as systolic blood pressure < 90 mmHg on two sequential readings at least 4 hours apart
• Pregnant or breastfeeding
• Concurrent dual antithrombotic therapy (aspirin or P2Y12 inhibitor plus anticoagulation to treat deep venous thrombosis or pulmonary embolism (single antiplatelet or anticoagulant agent at prophylaxis or therapeutic dose is permitted)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times upper limit of normal, hemoglobin < 8 grams per deciliter (g/dL), or platelets <50,000 per cubic millimeter (mm3)
• History of recent major bleeding, defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis (ISTH).
• Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dipyridamole 100 Milligram(mg); 100 milligrams (mg) by mouth (PO) four times a day (QID)	Drug: Dipyridamole 100 Milligram(mg); Drug will be given for 14 days while in the hospital.
Placebo Comparator: Placebo; Placebo given by mouth four times a day	Drug: Placebo oral tablet; Placebo will be given for 14 days while in the hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in D-dimer	average percent daily change in plasma D-dimer levels compared to baseline	baseline, up to approximately 14 days after last study drug administration
Number of Participants With Wins at Each Level of a Hierarchical Composite Rank Score	Compare each dipyridamole patient head to head against each placebo patient using a hierarchical composite rank score; death; days on mechanical ventilation; dichotomized (yes/no) decrease in daily average SpO2/FiO2 of at least 50 units relative to day 1 at anytime during the observation period; cumulative sum of COVID ordinal score during study hospitalization. Ordinal scores could range 1-8. Levels 1 and 2 imply no hospitalization and 8 is the worst possible score (death); by definition, the subjects in the DICER study were hospitalized during the time period in which the study observed their ordinal scores.	up to approximately 30 days after hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days Alive and Free of Organ Support	Organ support is defined as receipt of invasive mechanical ventilation, vasopressor therapy, ECMO support, or dialysis.	up to approximately 28 days after last study drug administration score
Individual Component of Composite Endpoint- Death	Death of any cause during duration of study participation	up to approximately 30 days after hospital discharge
Individual Component of Composite Endpoint- Days on Mechanical Ventilation	The number of days spent on invasive mechanical ventilation during study hospitalization.	up to 14 days after study drug administration
Individual Component of Composite Endpoint- Sp02/Fi02 (as Shown by Participant Count)	Binary outcome indicating patients whose Sp02/Fi02 dropped 50 points relative to baseline at any time during hospitalization.	up to 14 days after study drug administration
Individual Component of Composite Endpoint- Cumulative Ordinal Score	Cumulative sum of WHO Ordinal Scale for Clinical Improvement scores during hospitalization or through 14 days after study drug administration, whichever occurs first. The WHO Ordinal Scale ranges from 1 (no limitation of activities) through 8 (death). By definition, hospitalized patients score 3 or higher on the scale. The equation can be written: Cumulative Ordinal Score = (days in hospital up to 14) x (average ordinal score during hospitalization). Higher scores represent a combination of worse outcomes and longer hospitalizations.	Hospitalization up to 14 days after study drug administration

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Jason Knight, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2020
• Primary Completion (Actual): February 22, 2021
• Study Completion (Actual): February 22, 2021

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 18, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Oxygen
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Coronavirus Infections; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Phosphodiesterase Inhibitors; Dipyridamole
• Other Study ID Numbers: HUM00179783

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No